Clinical Antipsychotic Trials

Lieberman JA, Stroup TS, McEvoy JP, et al. Clinical antipsychotic trials of intervention effectiveness (CATIE) investigators. Effectiveness of antipsychotic drugs in people with chronic schizophrenia. N Engl J Med 2005 353 1209-1223. 

Meyer, J. M., Nasrallah, H. A., McEvoy, J. P., Goff, D. C. et al. (2005). The clinical antipsychotic trials of intervention effectiveness trial clinical comparison of subgroups with and without metabolic syndrome. Schizophr. Res., 80, 9-18. 

The African-American Heart Failure Trial showed that a large number of African Americans can be recruited in sufficient numbers with enough power to show efficacy in a clinical trial. In psychiatry the large START) study of depression was made up of 24% minorities (Trivedi etal, 2006). The recently completed Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was able to recruit enough African Americans to make up about one third of its participants (Stroup et al, 2006). 

The Clinical Antipsychotic Trials of Intervention Effectiveness study showed that olanzapine, compared with quetiapine, risperidone, ziprasi-... 

CATIE Clinical antipsychotic trial of intervention effectiveness... 

CLINICAL ANTIPSYCHOTIC TRIALS OF INTERVENTION EFFECTIVENESS (CATIE)... 

As already noted, in the clinical antipsychotic trials of intervention effectiveness among adults exposed to older neuroleptics and several atypicals (Nasrallah, 2007), no difference was found between the older antipsychotic drugs and the newer ones in regard to producing extrapy-ramidal effects, movement disorders, or akathisia. 

The CATIE project will evaluate the clinical effectiveness of atypical antipsychotics in the treatment of schizophrenia and of Alzheimer s disease. Although antipsychotics were first introduced for the treatment of schizophrenia, they are now used for many other disorders. It is unclear how effective they are and, most important, in view of their rather high cost, how favorably they compare to the first generation of antipsychotics, all of which are available in generic (and thus much less expensive) forms. The CATIE (Clinical Antipsychotic Trials in Intervention Effectiveness) study has specific aims, including the determination of long-term effectiveness and tolerability of the atypical antipsychotics, compared to each and to a typical or classic antipsychotic. At this... 

McEvoy JP, Meyer JM, Goff DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res 2005 80 19-32. 

Wessels AM, Pollock BG, Anyama NG, Schneider LS, Lieberman JA, Marder SR, Bies RR. Association of 9-hydroxyrisperidone concentrations with risk of switching or discontinuation in the clinical antipsychotic trial of intervention effectiveness-Alzheimer s disease trial. J Clin Psychopharmacol 2010 30 683-7. 

Changes in the 10-year risk of coronary heart disease have been compared between treatment groups in 1125 patients followed for 18 months or until treatment discontinuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) in schizophrenia [22 ]. The mean change in 10-year coronary heart disease risk differed significantly between treatments. Olanzapine was associated with a 0.5% increase and quetiapine with a 0.3% increase, while the risk fell in patients who used perphenazine (-0.5%), risperidone (—0.6%), and ziprasidone (—0.6%). The difference in 10-year coronary heart disease risk between olanzapine and risperidone was statistically significant. 

Miller DD, Caroff SN, Davis SM, Rosenheck RA, McEvoy JP, Saltz BL, Riggio S, Chakos MH, Swartz MS, Keefe RS, Stroup TS, Lieberman JA. Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Extrapyramidal side-effects of antipsychotics in a randomised trial. Br J Psychiatry 2008 193(4) 279 8. 

Table 5-27 and Table 5-28 summarize the clinically relevant pharmacokinetic and pharmacodynamic properties of other novel antipsychotics ( 326). Drug interactions with these agents were not systematically evaluated because controlled clinical trials usually prohibit concurrent medications. There are also many special circumstances (e.g., patients with comorbid medical diseases, substance abuse, epilepsy, or atypical indications such as agitation associated with mental retardation or dementia) that are not usually addressed in clinical research trials. Thus, much remains to be learned about significant drug interactions in these patient groups. To our knowledge, however, no consistent, serious, clinically relevant interactions have been reported. 

Although atypical antipsychotic agents may cost several times as much as traditional antipsychotics, drug costs in schizophrenia account for only 1-4% of the total treatment cost (Knapp, 1997). The argument then is that a small increase in drug costs— say to 10% of total cost—may result in disproportionate savings in the highly expensive direct hospital costs, if clinical trial... 

To date, clozapine remains the only drug with proven and superior efficacy in treatment-resistant patients, and it is currently the only drug approved for the treatment-resistant schizophrenic. Studies have shown a response of approximately 30% to 50% in these well-defined treatment-resistant patients. Clinical trials have consistently found clozapine to be superior to traditional antipsychotics for treatment-refractory patients, and it is efficacious even after nonresponse to other SGAs and in partially responsive patients. It is often rapidly effective even in those who have had a poor response to other medication for years. Recent studies have demonstrated that it has a beneficial effect for aggression and suicidality, which led to the Food and Drug Administration (FDA) approval for the treatment of suicidal behavior in people with psychosis.41... 

Research in psychopharmacology has shown that ethnicity must be considered in psychiatry as well (Lawson, 1986 Pi 8c Simpson, 2005). Early clinical trials with antipsychotic and antidepressant medications showed that ethnic minorities may respond when given the same doses as Caucasians, and may have more side effects (Lawson, 1986 Lawson, 1990). However, dosing cannot be used as a measure of appropriate pharmacotherapy because an extensive literature has shown that African Americans often receive higher doses of antipsychotics despite evidence of more side effects. 

Green, M. F. Braff, D. L. (2001). Translating the basic and clinical cognitive neuroscience of schizophrenia to drug development and clinical trials of antipsychotic medications. Biol. 

Collaborative Working Group on Clinical Trial Evaluations. (1998). Measuring outcome in schizophrenia differences among the atypical antipsychotics. 

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